The objective of this research proposal is to study in vitro steroidogenic and non-steroidogenic interactions between granulosa and theca cells of human, porcine, hamster, rat and rabbit follicles. We have observed an interaction between granulosa cells and theca from human and hamster follicles that results in a synergistic production of progesterone. A portion of this proposal is concerned with describing experiments which will yield information as to the mechanism controlling synergistic progesterone synthesis. Non-steroidogenic interactions between granulosa cells and theca have also been observed. First, human, hamster and porcine granulosa cells respond with significantly greater growth rates in vitro when cultured with theca or spent media from thecal cultures. Preliminary evidence indicates a protein growth factor is involved. Second, hamster cells co-cultured with theca undergo dramatic changes in shape, similar to those seen after stimulation with gonadotropins. Experiments are described which will attempt to charcterize the nature of the thecal growth factor, and its possible relationship to follicular atresia. Other experiments are described which will yield information to determine 1: whether human cells undergo thecal induced shape changes, 2: the cytoskeletal characteristics of the granulosa cells which are associated with cell shape change seen in these cells, 3: the nature of the thecal factor controlling cell shape, and 4: the relationship of the functional state of the granulosa cell and shape changes.